title: Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma.
abstract: BACKGROUND
  There is currently no curative therapy for cutaneous T cell lymphoma (CTCL). New therapies are therefore needed. Telomerase, the enzyme that allows for unrestricted cell divisions of cancer cells, is a promising target for cancer therapy. The telomerase-specific peptide vaccination GV1001 has shown promising results in previous studies. Since telomerase is expressed in malignant cells of CTCL, GV1001 vaccination in CTCL is a promising new therapeutic approach.
  
  
  OBJECTIVE
  We sought to investigate the efficacy of GV1001 vaccination in CTCL patients and characterize the induced immune response.
  
  
  METHODS
  Six CTCL patients were vaccinated with the GV-peptide using granulocyte/macrophage colony-stimulating factor as adjuvant. Objective clinical response and the T cell response were assessed.
  
  
  RESULTS
  None of the patients demonstrated objective clinical response to the vaccination whereas one patient showed disease progression. 1/6 patients acquired a GV1001-specifc T cell response with a Th1 cytokine profile and expression of skin-homing receptors. This hTERT-specific T cell response was not associated with beneficial modulation of the tumor-infiltrating leukocytes. Furthermore, removal of regulatory T cells did not enhance responsiveness to GV1001 in vitro in any of the patients analyzed.
  
  
  CONCLUSIONS
  Our results suggest that the GV1001 vaccination is not effective in CTCL patients and disease progression in 1/6 patients raises concerns about its safety. By analyzing skin-homing properties of GV1001-specific T cells and the involvement of regulatory T cells we nevertheless provide insight into vaccine-induced immune responses which may help to improve vaccine strategies in CTCL.
authors.affiliation: Department of Dermatology, Inselspital, University of Bern, 3010 Bern, Switzerland. schlapbach@gmx.net
authors.forename: Christoph
authors.initials: C
authors.lastname: Schlapbach
authors.forename: Daniel
authors.initials: D
authors.lastname: Yerly
authors.forename: Barbara
authors.initials: B
authors.lastname: Daubner
authors.forename: Nikhil
authors.initials: N
authors.lastname: Yawalkar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hunger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007107:Immune System; D016410:Lymphoma, T-Cell, Cutaneous / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D019098:Telomerase / Q000378:metabolism*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; D010455:Peptides; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C514987:GV1001 peptide; D019098:Telomerase